The purpose of this study was to identify the mediating effects of emotional stability and social support in the relationship between major satisfaction and academic adjustment of college freshmen majoring in nursing and health science. Data were collected from 291 college freshmen majoring in nursing and health science using a self-reported questionnaire, which included a major satisfaction, emotional stability, social support, and academic adjustment. A Descriptive, t-test, ANOVA, Pearson correlation, hierarchical regression, and Sobel test were used for data analysis. The result showed that major satisfaction was positively related to emotional stability, social support, and academic adjustment. Emotional stability and social support was positively related to academic adjustment. Hierarchical regression analysis showed that emotional stability partially mediated the relationship between major satisfaction and academic adjustment. Also, social support partially mediated the relationship between major satisfaction and academic adjustment. These results suggest that emotional stability and social support can be effective variables in improving academic adjustment of freshmen majoring in nursing and health science. Overall, it is necessary to develop mental health interventions and networking system including strategies to improve emotional stability and social support in order to facilitate their academic adjustment.